Cell Junctions and Adhesion Flashcards
Epithelial Cell structure
lateral domain connecting cell to other cells, basal domain sitting on basement membrane
Types of cell junctions
Tight junction
Zona
Tight junctions
Zona occludens
Encircle cell
Look like branches/interconnected sealing ridges in freeze fracture
Look like just tightly packed first part of cells touching in EM
Sealing strands
two membranes are tightly linked together by lines of transmembrane proteins
-kissing point -end of edge where two cells are touching
Occluding and Claudins
Mediate adhesion at tight junctions
Linked through adaptor proteins like ZO-1 to attach to actin cytoskeleton
Belt desomosmes
Zonula Adherens/Adeherens junction
Encircle cell and are positioned right under tight junctions
Actomyosin complex undergoes contraction to buckle epithelium to make tighter
Cadherins
Transmembrane proteins that mediate adhesion at belt desmosomes
Need 4 calciums to function-extracellular tail
Histdine, valine, alanine sequence facilitates formation of cadherin cis homophilic dimeres
Can also make trans dimers to attach two PMs
Cytoplasmic tail interacts with actin filaments using catenin proteins
Catenin proteins
3 proteins that exist in cytosol and attach cadherins to to actin-form catenins complex with actin
beta binds to caderhin and gamma, and alpha binds to actin
Beta catenin is transcriptional cofcator
E-cadherin
needed for tight junction formation
loss results in endothelial -mesynchemal transfoarmtion during cancer
results in cell polarity, stationarity, and cell adhesive abilities
Spot Desmosomes
Macula Adherens, Desmosomes
spot-like cell-cell junctions
Linked to keratin intermediate filaments achored to desmoplankin
Outer dense plaque, inner dense bplaue, dense middle line
Desmocollins and desmogleins
Cadherin family proteins that mediate adhesion at spot desmosomes-these are in plaques
Integrins
transmembrane proteins that have an α subunit and a βsubunit
Interact with ECM proteins on RGD peptide sequence
Present in actin-linked cell-matrix adhesion sites-focal adhesions
Bind ECM and internal cytoskeleton
alpha and beta subunit of integrin
alpha-two chains linked by disulfide linkage and globular head with binding sites for divalent cations
beta-extracellular chain with cysteine rich regions
- intracellular portion interacts with actin filaments through three connecting proteins
- talin, vinculin, and alpha actinin
Hemidesmosomes
Mediate interaction between cells and basement membrane
-using integrin alpha6beta4
Linked to intermediate filaments
BPG and Plectin
Consist of a plate and a plaque with keratin intermediate filaments entering PM
integrin alpha6beta4
Mediate interaction between cells and basement membrane
Focal adhesions/contacts
integrin mediated
Linked to actin cytoskeleton
Not seen without immune EM
Important for cellular processing such as migration
vinculin and talin
Gap junctions
Coordinate cellular rresponses
Formed by connection channels
Allow small molecules like Ca and cAMP to pass cell to cell
Connexin
6 connexin monomers form hexameric connexon-central open channel
Transmembrane protein
-when connexons align with connexons in adjacent cell-get hydrophilic intercellular channel
Both connections have to be open
Connexon permeability
Open with low Ca+, closed with high (and signals apoptosis)
also can be pH or voltage gated among other things
Gap junctions in pics
PM’s are extremely lose together
-but can be very extensie structures (unlike tight junctions)
Tight junction mutation
Claudin 16
auto recessive
renal disorder
Belt desmosome mutation
p-cadherin
Early hair loss and progressive central retina degeneration
Spot desmosome mutation
Autoimmune disease with antibodies against desmoglein 1
blistering disease
cause splitting (basically empty space-vesicle)within the epidermal cell layers
Hemidesmosomes mutation
Autoimmune with antibodies against BPAG1 and 2-blistering disease
cause splitting (basically empty space-vesicle) between the epidermis and the underlying basement membrane
Gap junction mutation
Mutations in multiple different connections assocaited with deafness
Blistering diseases defects + facts
spot desmosomes or hemidesmosomes
-loss of adhesion of keratinocytes in superficial layers of the epidermis-pemphigus foliaceus
Antibody triggers resoponse to eosinophil chemitactic factor, the eosinophils release proteases to breadown anchoring filaments
Non-junctional adhesion mechanisms
Dynamic cell adhesions-found during cell locomotion where dynamic cell-cell and cell-matrix adhesions are needed
-adhesions are not always at stable junctions
also for inflammation and immune response
selectins
transmembrane proteins that bind oligosaccharides
Ca regualated conformation and ability to bind to carbs-binds to CRD
Expressed on surface of lymphocytes, endothelial cell, and platelets
Carbohydraterich domain (CRD)-binds to sugar
3 types of selectins
L-carried by lymthoctes and bind to sulfated carbs
E-expressed by activated endothelial cells
P-expressed by platelets and activated endothelial cells
Immunoglobulin superfamily
IgCAMs-Ig like domains on extracellular side
Ca independent
Extracellular segment of a cell adhesion molecule
Ig molecules bind either homophilically (same exact molecule) or heterophilically (any ig molecule)
ICAM and VCAM
play important role in the homing process
Leukocyte extravasation process
Leukocytes slow and and start rolling on endothelial cell surface though loose adhesion with selections binding to carbs on leukocyte cell surface
During rolling, integrins on leukocytes are activated to bind to ICAM and VCAM on endothelial cells
-Stronger interactions slow down and arrest leukocytes on cell surface
Integrin mediated migration of leukocytes through wall of blood vessel, in between the end cells
This looks like a cell is where it should not be in pictures
Dynamic assembly and disassembly of adhesions
Very important for cell migration
Can be intern mediated adhesions
Tight junctions
Belt desmosomes
Spot desmosomes
hemidesmosomes
focal adhesion
gap junctions
transmembrane protein and cytoskelton for each
occludins/claudins, actin
cadherins
actin
Cahderins (desmocollins/desmogleins) intermediate filaments
integrin alpha 6beta 4
intermediate filaments
integrins
actin
connexins
none
